1. Field of the Invention
The invention relates to a new method of preparing quinolines, naphthyridines and other nitrogen bi-heterocyclic compounds of the general formula ##STR2##
These nitrogen bi-heterocyclic compounds are known from the literature.
2. Discussion of Prior Art
Organ. Synthesis, Vol. III, p. 272 presents a review of a number of syntheses, especially of 4,7-dichlorquinoline. For example, according to J. Amer. Chem. Soc. 68 (1946), 113, 4-hydroxy-7-halogen-quinoline is prepared from the corresponding 2-carbethoxy derivative, and, according to J. Amer. Chem. Soc. 68 (1946), 1204, 4-hydroxy-7-chlorquinoline is prepared from the 3-carbethoxy derivative in two separate stages by alkaline hydrolysis, separation of the solid from the carboxylic acid by filtration, and decarboxylation of the latter in mineral oil. According to J. Med. Chemistry 21 (1978), 268, the production of 6-, 7- or 8-halogen-4-hydroxyquinolines, and, according to J. Heterocycl. Chem. 11 (1974), 849, the production of 4-hydroxyquinolines methoxylated in the 6th position or ethoxylated in the 7th position, is accomplished, again by alkaline saponification and by decarboxylation in high-boiling solvents, after an intervening isolation of the acid. 4-Oxo-6-methyl-6,7,8,9-tetrahydro-homopyrimidazole has also been synthesized by alkaline saponification followed by decarboxylation, according to Arzneimittelforschung 22 (1972), 815. From U.S. Pat. No. 3,856,800 it is apparent that 4-hydroxy-7-methyl-naphthyridine-1,8 can be prepared by means of first stages of an N-oxide from which the oxygen has to be removed again at the end by hydrogenolysis. Boiling 18% hydrochoric acid has been used for the hydrolysis of 3-carbethoxy-4-hydroxy-6-methoxyquinoline according to J. Amer. Chem. Soc. 68 (1946), 1204, and of 5-hydroxy-6-carbethoxy-naphthyridine-1,7 according to Liebigs Ann. Chemie 4 (1979), 443. In the case of the latter compound, decarboxylation to 5-hydroxy-naphthyridine-1,7 occurred, which then had to be purified by sublimation.
These known methods of preparation have in common the necessity to use at least a stoichiometric amount of alkali or hydrochloric acid, which then has to be neutralized, resulting in large amounts of salt solutions, which today create disposal problems.
It is furthermore disadvantageous that these syntheses are two-step syntheses on account of the isolation and washing of the acid prior to the decarboxylation, resulting in high costs when the method is applied on a large production scale.
It, therefore, became desirable to provide a method which produces little waste, is easy to perform, and nevertheless gives good yields and purities in the final products. The solution of this problem is described hereinbelow.